Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
ICAR-National Institute of High Security Animal Diseases, Bhopal, Madhya Pradesh, India.
J Biomol Struct Dyn. 2021 Sep;39(15):5668-5681. doi: 10.1080/07391102.2020.1790425. Epub 2020 Jul 8.
SARS-CoV-2 is the causative agent of COVID-19 and has been declared as pandemic disease by World Health Organization. Lack of targeted therapeutics and vaccines for COVID-2019 have triggered the scientific community to develop new vaccines or drugs against this novel virus. Many synthetic compounds and antimalarial drugs are undergoing clinical trials. The traditional medical practitioners widely use Indian medicinal plant (Ashwagandha) natural constituents, called withanolides for curing various diseases. The main protease (M) of SARS-CoV-2 plays a vital role in disease propagation by processing the polyproteins which are required for its replication. Hence, it denotes a significant target for drug discovery. In the present study, we evaluate the potential of 40 natural chemical constituents of Ashwagandha to explore a possible inhibitor against main protease of SARS-CoV-2 by adopting the computational approach. The docking study revealed that four constituents of Ashwagandha; Withanoside II (-11.30 Kcal/mol), Withanoside IV (-11.02 Kcal/mol), Withanoside V (-8.96 Kcal/mol) and Sitoindoside IX (-8.37 Kcal/mol) exhibited the highest docking energy among the selected natural constituents. Further, MD simulation study of 100 ns predicts Withanoside V possess strong binding affinity and hydrogen-bonding interactions with the protein active site and indicates its stability in the active site. The binding free energy score also correlates with the highest score of -87.01 ± 5.01 Kcal/mol as compared to other selected compounds. In conclusion, our study suggests that Withanoside V in Ashwagandha may be serve as a potential inhibitor against M of SARS-CoV-2 to combat COVID-19 and may have an antiviral effect on nCoV.Communicated by Ramaswamy H. Sarma.
SARS-CoV-2 是 COVID-19 的病原体，世界卫生组织已宣布其为大流行病。针对 COVID-19 缺乏靶向治疗和疫苗，促使科学界开发针对这种新型病毒的新疫苗或药物。许多合成化合物和抗疟药物正在进行临床试验。传统的医疗从业者广泛使用印度药用植物（ Ashwagandha ）天然成分，称为 Withanolides ，用于治疗各种疾病。SARS-CoV-2 的主要蛋白酶（M）在通过处理复制所需的多蛋白来传播疾病方面起着至关重要的作用。因此，它是药物发现的重要靶标。在本研究中，我们通过采用计算方法评估 Ashwagandha 的 40 种天然化学成分的潜力，以探索针对 SARS-CoV-2 主要蛋白酶的可能抑制剂。对接研究表明， Ashwagandha 的四种成分； Withanoside II （-11.30 Kcal/mol ）， Withanoside IV （-11.02 Kcal/mol ）， Withanoside V （-8.96 Kcal/mol ）和 Sitoindoside IX （-8.37 Kcal/mol ）在所选天然成分中表现出最高的对接能。进一步， 100 ns 的 MD 模拟研究预测 Withanoside V 与蛋白质活性位点具有强烈的结合亲和力和氢键相互作用，并表明其在活性位点中的稳定性。结合自由能评分也与最高评分-87.01 ± 5.01 Kcal/mol 相关，与其他选定的化合物相比。总之，我们的研究表明， Ashwagandha 中的 Withanoside V 可能作为 SARS-CoV-2 的 M 的潜在抑制剂，用于对抗 COVID-19 ，并可能对 nCoV 具有抗病毒作用。由 Ramaswamy H. Sarma 传达。
